1. Field of the Invention
The present invention relates to novel compounds that exhibit progesterone antagonism without any sign of partial agonistic activity. Such compounds have application in fertility control and the treatment of hormone dependent breast cancer. The present invention also relates to processes of preparation and the use in therapy of such novel compounds.
2. Description of the Relevant Art
In the past, progesterone antagonists have been postulated to be of potential benefit in the treatment of a variety of diseases including breast cancer and different forms of fertility control.
Up to now, only two compounds belonging to this class have been approved for clinical use. The prototype antagonist, Mifepristone (see FIG. 1), is indicated for the induction of abort and Ulipristal is approved for postcoital fertility control.
Both compound are characterized as progesterone receptor modulators indicating that there might be a partial agonistic component contributing to their overall activity.
Compounds that lack any partial agonistic activity whatsoever should exhibit a greater activity in the approved indications and potentially also in the treatment of breast cancer.

There is the general understanding that the substituent in the 11′ position is responsible for the progesterone receptor profile (Nickisch et al Steroids Vol 78, 255-267, 2013). Whereas the dimethyl amino group as found in Mifepristone and Ulipristal leads to compounds with a predominant antagonistic activity, aromatic substituents like furans or pyridins lead to compounds with a strong partial agonistic component (EP000002417148) that have potential in the treatment of gynecological indications like endometriosis but not for postcoital fertility control and breast cancer.
Substituents in the 17 position have an influence on the binding selectivity for the progesterone and glucocorticoid receptor. 17 moieties have been reported to lead to a high selectivity for the progesterone receptor are e.g. the perfloualkyl alkyl group as originally described in DE 197 06061.Different 11 substituents carrying the perfluoralkyl group in the 17 position have been reported later e.g. WO 2008058767, WO 2011005929, WO 2011009530, WO 2011009531, WO 2011009534, WO 2011098436 and WO 2011098437.Other 17 substituents with good specificity to the progesterone receptor include 17-spirofuran-3′-ylidene as described in EP 549041, 17 spirolactones as described in EP 558416 and difluro 17-spirofuran-3′yliden as described in WO 20100118025.In those patents a large variety of 11′ substituents including different heteroycles have been described, but surprisingly 11′N imidazols have not been reported, lost likely caused by the fact that such molecules need special methods for their synthesis, although the general structure has been claimed by Cook et al. In WO99/45022.It was therefore even more surprising that the described 11′N Imidazols exhibit very potent antiprogestational activity lacking any agonistic component, what make them ideal candidates for the induction of labor, postcoital fertility control, termination of pregnancy and breast cancer